Expression of the multidrug resistance, MDR1, gene in neuroblastomas.
Metastatic neuroblastoma is a childhood malignancy that is frequently responsive to chemotherapy with doxorubicin, vincristine, and teniposide (VM26), among other drugs, but in the majority of treated patients, the tumor recurs during or after chemotherapy. In this work, we have examined the hypothesis that the development of resistance to chemotherapy in neuroblastoma might be related to the expression of the human MDR1 gene, which encodes a multidrug transporter that functions as an energy-dependent drug efflux pump. RNA samples from 49 neuroblastomas were analyzed, including 31 from untreated and 18 from treated patients. MDR1 RNA was detectable in the majority of treated and untreated tumors using a sensitive, semiquantitative slot blot assay. Of the samples from treated patients, five of 18 were found to have high MDR1 RNA levels, whereas only three of 31 from untreated patients had high MDR1 levels, a statistically significant difference (P less than .01). These results show that high levels of MDR1 RNA are often associated with resistance to chemotherapy in neuroblastoma and suggest that they may contribute to this resistance. Many of the neuroblastoma samples were also evaluated for N-myc amplification but there was no correlation between N-myc copy number and the level of MDR1 mRNA expression.
Goldstein
L J
LJ
Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Fojo
A T
AT
Ueda
K
K
Crist
W
W
Green
A
A
Brodeur
G
G
Pastan
I
I
Gottesman
M M
MM
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000037:antagonists & inhibitors*; D002460:Cell Line; D002648:Child; D004351:Drug Resistance / Q000235:genetics; D005784:Gene Amplification / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D009447:Neuroblastoma / Q000032:analysis / Q000188:drug therapy / Q000235:genetics*; D009857:Oncogenes; D012333:RNA, Messenger / Q000032:analysis / Q000302:isolation & purification; D012334:RNA, Neoplasm / Q000032:analysis / Q000302:isolation & purification; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm